6-72197050-A-G

Variant names:

• chr6-72197050-A-G
• rs2249625
• NM_014989.7:c.1678+13901A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014989.7(RIMS1):​c.1678+13901A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 151,908 control chromosomes in the GnomAD database, including 22,770 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (22770 hom., cov: 31)
• Consequence: RIMS1 NM_014989.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.707
• Publications: 4 publications found

Genes affected

RIMS1 (HGNC:17282): (regulating synaptic membrane exocytosis 1) The protein encoded by this gene is a RAS gene superfamily member that regulates synaptic vesicle exocytosis. This gene also plays a role in the regulation of voltage-gated calcium channels during neurotransmitter and insulin release. Mutations have suggested a role cognition and have been identified as the cause of cone-rod dystrophy type 7. Multiple transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Mar 2012]

RIMS1 Gene-Disease associations (from GenCC):

• cone-rod dystrophy 7

  Inheritance: AD Classification: STRONG, LIMITED, NO_KNOWN Submitted by: G2P, Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIMS1	NM_014989.7	c.1678+13901A>G		intron_variant	Intron 6 of 33	ENST00000521978.6	NP_055804.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIMS1	ENST00000521978.6	c.1678+13901A>G		intron_variant	Intron 6 of 33	1	NM_014989.7	ENSP00000428417.1

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79820 AN: 151790 Hom.: 22730 Cov.: 31

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.522

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.526 AC: 79929 AN: 151908 Hom.: 22770 Cov.: 31 AF XY: 0.525 AC XY: 38957 AN XY: 74220

African (AFR) AF: 0.729 AC: 30188 AN: 41436

American (AMR) AF: 0.548 AC: 8350 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1478 AN: 3468

East Asian (EAS) AF: 0.825 AC: 4248 AN: 5148

South Asian (SAS) AF: 0.485 AC: 2332 AN: 4810

European-Finnish (FIN) AF: 0.383 AC: 4048 AN: 10570

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27530 AN: 67920

Other (OTH) AF: 0.525 AC: 1107 AN: 2110

Alfa AF: 0.468 Hom.: 10354

Bravo AF: 0.551

Asia WGS AF: 0.680 AC: 2365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.0
DANN	Benign	0.86
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2249625; hg19: chr6-72906753;